Chemical profiling and evaluation of toxicological, antioxidant, anti-inflammatory, anti-nociceptive and tyrosinase inhibitory potential of Portulacaria afra using in-vitro, in-vivo and in-silico studies

Portulacaria afra Jacq (Portulacaceae) is a medicinal plant used traditionally in the treat-ment of pain and inflammation. This study aimed to evaluate the phytochemical composition, tox-icity, antinociceptive, and enzyme inhibition potential of P. afra. The methanol extract (PAME) was prepared through maceration and fractionated with ethanol to ethanol fraction of P. afra (ETPA). Both PAME and ETPA were found to be rich in total phenolic (TPC) and total flavonoid contents (TFC). Similarly, PAME showed the highest antioxidant potential through ABTS 93.16 +/- 0.05 mg TE /g of dry extract (D.E.) while ETPA showed maximum results (462 +/- 1.44 mg TE/g) in the CUPRAC method. The RP-UHPLC-MS analysis of PAME showed tentative identi-fication of 101 compounds in the positive mode and 14 compounds in the negative mode of ioniza-tion while GC-MS profiling gave a total of 15 compounds. The acute oral toxicity study of PAME revealed the safety and biocompatibility of the extract up to a dose of 5000 mg/kg orally in rats. In -vitro data revealed that varying concentrations of P. afra significantly (p < 0.05) inhibited heat -induced BSA denaturation compared to indomethacin in a concentration-dependent manner. PAME suppressed carrageenan-induced paw edema at the 4th hr with maximum inhibition. The analgesic efficacy of PAME was determined by the hotplate, writhing method, and tail-flicking rat models. In the hot plate method, PAME treated groups showed a significant effect (p < 0.0001). While in the writhing model, the PAME treated groups showed a significant (p < 0.0001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg compared to the control group. Similarly, PAME treated groups in the tail flicking model showed a significant (p < 0.001) anti-nociceptive effect at 200 mg/kg and 400 mg/kg. A dose-dependent increase in latency time (8.78 +/- 0.090 at (30 min), 11.39 +/- 0.005 at (60 min), 12.14 +/- 0.01 at (90 min) 15.19 +/- 0.03 at (120 min), p < 0.0001 was observed, compared to the control group. Similarly, the extract and frac-tion showed significant inhibitory potential against tyrosinase in in vitro and in-silico studies. Con-clusively the current study unveiled P. afra as a novel non-toxic source with good total antioxidant -mediated anti-inflammatory and analgesic potential.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).